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通过天然糖肽分子识别实现类似血肿的动态水凝胶化用于感染性骨折修复。

Hematoma-like dynamic hydrogelation through natural glycopeptide molecular recognition for infected bone fracture repair.

作者信息

Wang Shenghao, He Wenbo, Wang Huan, Liu Dachuan, Wang Miao, Yang Huilin, Pan Guoqing, Li Bin

机构信息

Orthopedic Institute, Department of Orthopaedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215006, China.

Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.

出版信息

Bioact Mater. 2023 Jul 26;30:73-84. doi: 10.1016/j.bioactmat.2023.07.018. eCollection 2023 Dec.

Abstract

Infected bone fractures remain a major clinical challenge for orthopedic surgeons. From a tissue regeneration perspective, biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired, while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research. Hematoma, the gel-like blood coagulum, plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing. In light of this, we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study. The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin (Van) and its target dipeptide D-Ala-D-Ala (AA), which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide (OGP). In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria, improve bone regeneration and restore the local inflammatory microenvironment. Together, findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.

摘要

感染性骨折仍然是骨科医生面临的一项重大临床挑战。从组织再生的角度来看,具有抗菌和骨诱导活性的生物材料支架备受期待,而能够模拟感染组织愈合过程中病理微环境的先进材料仍是一个值得深入研究的领域。血肿,即凝胶状的血凝块,在骨折修复中起着至关重要的作用,因为它能够作为一种动态的临时支架,携带细胞因子,用于清除病原体和促进组织愈合。鉴于此,在本研究中,我们设计了一种具有类似血肿抗菌或修复性能的动态水凝胶,用于感染性骨折的修复。所提出的动态水凝胶网络基于天然糖肽抗生素万古霉素(Van)与其靶标二肽D-Ala-D-Ala(AA)之间的可逆识别,通过引入内源性成骨肽(OGP),它可以作为类似血肿的支架,用于清除骨折区域的细菌并促进骨修复。体内实验表明,该水凝胶能够迅速根除细菌,促进骨再生并恢复局部炎症微环境。总之,本研究结果表明,使用类似血肿的动态水凝胶可能会引发针对易感性骨折手术策略的仿生革命。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/10413008/6c548c393f71/ga1.jpg

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